AbstractTwo brothers previously diagnosed as having α‐aminoadipic aciduria (α‐AA) were subjected to a tryptophan loading test to determine if their condition resulted from a defect in the α‐aminoadipate aminotransferase (kynurenine amino‐transferase) system. Normal increases in kynurenic and xanthurenic acids eliminated this possibility. Further analyses of their urines revealed that both boys had measurable amounts of previously undetected α‐ketoadipic acid (α‐KA) before and after the loading test. A reexamination of specimens from a prelysine and postlysine loading test reconfirmed the existence of α‐KA in their urines at the time the original observation of α‐AA was made. The response to the lysine load was a predictable increase in both α‐AA and α‐KA. The boy who had been referred to this institution with a learning defect responded to the tryptophan load with a slight decrease in α‐AA and an unpredicted decrease in α‐KA and 3‐hydroxykynurenine. His mentally normal brother showed a significant decrease in α‐AA and major increases in all other measured metabolites including α‐KA. The latter results were compatible with a defect in the oxidative decarboxylation of α‐KA. A comparison of the urinary α‐AA and α‐KA concentrations in our subjects with comparable data in mentally normal and mentally retarded patients with this condition suggeste